IP Library › Granted Patent US 7,423,156
Granted Patent B2
US 7,423,156 · App. 11/341,197 · Granted Sep 9, 2008

Preparation and use of aryl alkyl acid derivatives for the treatment of obesity

Assignee: Bayer Pharmaceuticals Corporation
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Quick Facts
Patent No.
US 7,423,156
App. No.
11/341,197
Granted
Sep 9, 2008
Kind
B2
Abstract

This invention relates to certain aryl alkyl acid compounds, compositions, and methods for treating or preventing obesity and related diseases.

Claims (189)

1. A compound of Formula (I)

wherein

Q is O or S;

A is a linker selected from

 wherein p is 1 or 2 and

 wherein m is 0 and n is 1, 2, 3, or 4, or

 m is 1 and n is 1, 2, or 3, and

wherein said linker is optionally substituted by one or two R 8 groups;

R 1 and R 2 are independently selected from hydrogen, halo, (C 1 -C 6 )alkyl, and (C 1 -C 6 )alkoxy;

R 3 is selected from hydrogen,

(C 1 -C 6 )alkyl optionally substituted by hydroxy, and

phenyl optionally substituted with (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, or halo;

R 4 is selected from hydrogen, nitro, and (C 1 -C 6 )alkyl; or

R 3 and R 4 may, when taken together with the carbon atoms to which they are attached, form a benzene ring optionally substituted with up to two substituents selected from halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, nitro, cyano, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, bis[(C 1 -C 6 )alkyl]aminocarbonyl, aminosulfonyl, (C 1 -C 6 )alkylaminosulfonyl, bis[(C 1 -C 6 )alkyl]aminosulfonyl, (C 1 -C 6 )alkylcarbonylamino, (C 1 -C 6 )alkylsulfonylamino, and hydroxy-(C 2 -C 6 )alkylaminocarbonyl, and

when two of said benzene ring substituents are (C 1 -C 6 )alkyl and are attached to adjacent carbon atoms of the benzene ring, they may be joined together to form a 5-7-membered carbocyclic ring;

R 6 is hydrogen;

R 7 is hydrogen or

(C 1 -C 6 )alkyl optionally substituted with (C 1 -C 6 )alkoxy, bis[(C 1 -C 3 )alkyl]amino or

phenyl optionally substituted with halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, or cyano; or

R 6 and R 7 are both (C 1 -C 6 )alkyl; or

R 6 and R 7 may form, together with the carbon atom to which they are attached, a 3- to 5-membered carbocyclic ring,

R 8 is (C 1 -C 6 )alkyl;

or a pharmaceutically acceptable salts or ester thereof.

2. The compound of claim 1 , wherein

Q is O;

A is

 wherein p is 1 or 2, and

 wherein said linker is optionally substituted by one or two R 8 groups;

R 3 and R 4 may, when taken together with the carbon atoms to which they are attached, form a benzene ring optionally substituted with up to two substituents selected from halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, nitro, cyano, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, bis[(C 1 -C 6 )alkyl]aminocarbonyl, aminosulfonyl, (C 1 -C 6 )alkylaminosulfonyl, bis[(C 1 -C 6 )alkyl]aminosulfonyl, (C 1 -C 6 )alkylcarbonylamino, (C 1 -C 6 )alkylsulfonylamino, hydroxy-(C 2 -C 6 )alkylaminocarbonyl; and

R 1 , R 2 , R 6 , R 7 , R 8 , and W are as defined in claim 1 .

3. The compound of claim 1 , wherein

Q is O;

A is

 wherein m is 0 and n is 1, 2, 3, or 4, or

 m is 1 and n is 1, 2, or 3, and

 wherein said linker is optionally substituted by one or two R 8 groups;

R 3 and R 4 may, when taken together with the carbon atoms to which they are attached, form a benzene ring optionally substituted with up to two substituents selected from halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, nitro, cyano, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, bis[(C 1 -C 6 )alkyl]aminocarbonyl, aminosulfonyl, (C 1 -C 6 )alkylaminosulfonyl, bis[(C 1 -C 6 )alkyl]aminosulfonyl, (C 1 -C 6 )alkylcarbonylamino, (C 1 -C 6 )alkylsulfonylamino, and hydroxy-(C 2 -C 6 )alkylaminocarbonyl, and

R 1 , R 2 , and R 8 are as defined in claim 1 .

4. The compound of claim 1 , wherein

Q is S;

A is

 wherein p is 1 or 2, and

 wherein said linker is optionally substituted by one or two R 8 groups;

R 3 and R 4 may, when taken together with the carbon atoms to which they are attached, form a benzene ring optionally substituted with up to two substituents selected from halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, nitro, cyano, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, bis[(C 1 -C 6 )alkyl]aminocarbonyl, aminosulfonyl, (C 1 -C 6 )alkylaminosulfonyl, bis[(C 1 -C 6 )alkyl]aminosulfonyl, (C 1 -C 6 )alkylcarbonylamino, (C 1 -C 6 )alkylsulfonylamino, and hydroxy-(C 2 -C 6 )alkylaminocarbonyl, and

R 1 , R 2 , R 6 , R 7 , R 8 , and W are as defined in claim 1 .

5. The compound of claim 1 , wherein

Q is S;

A is

 wherein m is 0 and n is 1, 2, 3, or 4, or

 m is 1 and n is 1, 2, or 3, and

wherein said linker is optionally substituted by one or two R 8 groups;

R 3 and R 4 may, when taken together with the carbon atoms to which they are attached, form a benzene ring optionally substituted with up to two substituents selected from halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, nitro, cyano, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, bis[(C 1 -C 6 )alkyl]aminocarbonyl, aminosulfonyl, (C 1 -C 6 )alkylaminosulfonyl, bis[(C 1 -C 6 )alkyl]aminosulfonyl, (C 1 -C 6 )alkylcarbonylamino, (C 1 -C 6 )alkylsulfonylamino, and hydroxy-(C 2 -C 6 )alkylaminocarbonyl, and

R 1 , R 2 , and R 8 are as defined in claim 1 .

6. The compound of claim 1 selected from the group consisting of:

4-[4′-(1,3-benzoxazol-2-ylamino)-1,1′-biphenyl-4-yl]-4-oxo-2-(2phenylethyl)butanoic acid;

2,2-dimethyl-4-{4′-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}4-oxobutanoic acid;

4-{4′-[(6-chloro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;

4-{4′-[(6-methoxy-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;

2,2-dimethyl-4-{4′-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxobutanoic acid;

2,2-dimethyl-4-{4′-[(4-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxobutanoic acid;

2,2-dimethyl-4-oxo-4-[4′-(5,6,7,8-tetrahydronaphtho[2,3-d][1,3]oxazol-2-ylamino)-1,1′-biphenyl-4-yl]butanoic acid;

4-{4′-[(5-fluoro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;

4-{4′-[(5-isopropyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;

2,2-dimethyl-4-oxo-4-{4′-[(5-propyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}butanoic acid;

trans-2-({4′-[(6-chloro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;

trans-2-({4′-[(6-methoxy-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

trans-2-({4′-[(5-fluoro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;

trans-2-({4′-[(5,6-dimethyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

trans-2-{[4′-(1,3-benzoxazol-2-ylamino)-1,1′-biphenyl-4-yl]carbonyl}cyclopentane-carboxylic acid;

trans-2-({4′-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

trans-2-({4′-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({4′-[(5-fluoro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({4′-[(6-chloro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({4′-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4yl}carbonyl)-cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({4′-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

trans-(1R,2R)-2-[(4′-{[5-(trifluoromethyl)-1,3-benzoxazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({4′-[(6-fluoro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

trans-(1S,2S)-2-({4′-[(6-fluoro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

trans-2-({4′-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclohexane-carboxylic acid

trans-2-({4′-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclohexane-carboxylic acid;

4-{4′-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxo-2-(2-phenylethyl) butanoic acid;

trans-2-({3′-fluoro-4′-[(6-methoxy-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

trans-2-({4′-[(6-chloro-1,3-benzoxazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({3′-fluoro-4′-[(6-fluoro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({3′-fluoro-4′-[(5-fluoro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({3′-fluoro-4′-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({3′-fluoro-4′-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4yl)}carbonyl)cyclopentane-carboxylic acid; and

trans-(1R,2R)-2-[(3′-fluoro-4′-{[5-(trifluoromethyl)-1,3-benzoxazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid.

7. The compound of claim 1 selected from the group consisting of:

4-[4′-(1,3-benzothiazol-2-ylamino)-1,1′-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoic acid;

4-{4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;

4-{4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;

2,2-dimethyl-4-oxo-4-[4′-(1,3-thiazol-2-ylamino)-1,1′-biphenyl-4-yl]butanoic acid;

4-[4′-(1,3-benzothiazol-2-ylamino)-1,1′-biphenyl-4-yl]-2-(2-methoxyethyl)-4-oxobutanoic acid;

4-{4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2-(2-methoxyethyl)-4-oxobutanoic acid;

4-{4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2-(2-methoxyethyl)-4-oxobutanoic acid;

trans-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4yl}carbonyl)cyclobutane-carboxylic acid;

trans-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;

4-{4′-[(5-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;

2,2-dimethyl-4-{4′-[(6-nitro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxobutanoic acid;

4-{4′-[(4-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;

trans-(1R,2R)-2-{[4′-(1,3-benzothiazol-2-ylamino)-1,1′-biphenyl-4-yl]carbonyl}cyclopentane-carboxylic acid;

trans-2-{[4′-(1,3-benzothiazol-2-ylamino)-1,1′-biphenyl-4-yl]carbonyl}cyclopentane-carboxylic acid;

4-{4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxo-2-(2-phenylethyl)butanoic acid;

2-(2-{4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2-oxoethyl)pentanoic acid;

trans-2-({4′-[(5-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;

trans-2-({4′-[(6-nitro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

trans-2-({4′-[(4-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

4-{4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2-[2-(dimethylamino) ethyl]-4-oxobutanoic acid;

2-[2-(dimethylamino)ethyl]-4-{4′-[(5-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl-}-4-oxobutanoic acid;

2-[2-(dimethylamino)ethyl]-4-{4′-[(6-nitro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxobutanoic acid;

trans-2-({4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

trans-2-({4′-[(6-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

trans-2-({4′-[(6-ethoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

trans-2-({4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

trans-(1S,2S)-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

2,2-dimethyl-4-{4′-[(5-nitro-1,3-thiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxobutanoic acid;

4-(4′-{[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino}-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoic acid;

trans-(1R,2R)-2-({4′-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;

trans-(1S,2S)-2-({4′-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

cis-3-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4yl}carbonyl)cyclohexane-carboxylic acid;

cis-3-({4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclohexane-carboxylic acid;

trans-2-[(4′-{[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]-cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({4′-[(6-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

trans-(1S,2S)-2-({4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

trans-(1S,2S)-2-({4′-[(6-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

trans-2-({4′-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

trans-2-({4′-[(4-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

trans-2-({4′-[(5-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

trans-2-[(4′-{[6-(trifluoromethyl)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]-cyclopentane-carboxylic acid;

trans-2-({4′-[(5-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

trans-2-({4′-[(5,7-dimethyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

trans-2-[(4′-{[6-(methylsulfonyl)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]-cyclopentane-carboxylic acid;

trans-2-({4′-[(5,6-dimethyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

4-{4′-[(6-ethoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;

4-{4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;

trans-2-({4′-[(5,7-difluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopentane-carboxylic acid;

trans-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopropane-carboxylic acid;

trans-(1R,2R)-2-[(4′-{[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)-carbonyl]cyclopentane-carboxylic acid;

trans-2-{[4′-(1,3-benzothiazol-2-ylamino)-1,1′-biphenyl-4-yl]carbonyl}cyclopropane-carboxylic acid;

trans-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclohexane-carboxylic acid;

trans-2-({4′-[(4-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopropane-carboxylic acid;

trans-2-({4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopropane-carboxylic acid;

trans-2-({4′-[(5,7-difluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopropane-carboxylic acid;

trans-2-({4′-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclopropane-carboxylic acid;

trans-2-{[4′-(1,3-benzothiazol-2-yl)amino)-1,1′-biphenyl-4-yl]carbonyl}cyclobutane-carboxylic acid;

trans-2-({4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclobutane-carboxylic acid;

trans-2-({4′-[(4-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl) cyclobutane-carboxylic acid;

trans-(1R,2R)-2-({4′-[(6-isopropyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

trans-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

trans-2-({3′-fluoro-4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-carbonyl)cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({3′-fluoro-4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;

trans-2-{[4′-(1,3-benzothiazol-2-yl)amino)-3′-fluoro-1,1′-biphenyl-4-yl]carbonyl}cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({4′-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}- carbonyl)cyclopentane-carboxylic acid;

trans-(1S,2S)-2-({4′-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}-carbonyl)cyclopentane-carboxylic acid;

trans-(1R,2R)-2-[(3′-fluoro-4′-{[6-(trifluoromethyl)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl)cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({3′-fluoro-4′-[(5-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({3′-fluoro-4′-[(4-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-carbonyl)cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({4′-[(5-chloro-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({3′-fluoro-4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({3′-fluoro-4′-[(6-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-carbonyl)cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({4′-[(5,7-dimethyl-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}-carbonyl)cyclopentane-carboxylic acid;

trans-(1R,2R)-2-({4′-[(5,7-difluoro-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;

trans-(1R,2R)-2-[(3′-fluoro-4′-{[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid;

trans-(1R,2R)-2-[(3′-fluoro-4′-{[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid;

trans-2-({3′-fluoro-4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclobutane-carboxylic acid;

trans-2-{[4′-(1,3-benzothiazol-2-ylamino)-3′-fluoro-1,1′-biphenyl-4-yl]carbonyl}cyclobutane-carboxylic acid;

trans-2-{[4′-(1,3-benzothiazol-2-ylamino)-3′-fluoro-1,1′-biphenyl-4-yl]carbonyl}cyclopropane-carboxylic acid;

trans-2-({3′-fluoro-4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopropane-carboxylic acid;

trans-(1R,2R)-2-({3′-fluoro-4′-[(6-isopropyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-carbonyl)cyclopentane-carboxylic acid;

trans-2-({3′-fluoro-4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;

trans-2-[(3′-fluoro-4′-{[6-(trifluoromethyl)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)-carbonyl]cyclopentane-carboxylic acid; and

4-{4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}-4-oxo-2-(2-phenylethyl)butanoic acid.

8. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or ester, in combination with a pharmaceutically acceptable carrier.

9. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or ester thereof, in combination with a pharmaceutically acceptable carrier and one or more pharmaceutical agents.

10. The pharmaceutical composition of claim 9 , wherein said pharmaceutical agent is an anti-obesity agent selected from the group consisting of β-3 agonists, CB-1 antagonists, nueropeptide Y5 inhibitors, appetite suppressants, and lipase inhibitors.

11. The pharmaceutical composition of claim 9 , wherein said pharmaceutical agent is an agent for the treatment of lipid disorders selected from the group consisting of HMG-CoA inhibitors, nicotinic acid, fatty acid lowering compounds, lipid lowering drugs, ACAT inhibitors, bile sequestrants, bile acid reuptake inhibitors, microsomal triglyceride transport inhibitors, and fibric acid derivatives.

12. The pharmaceutical composition of claim 9 , wherein said pharmaceutical agent is an anti-hypertensive agent selected from the group consisting of β-blockers, calcium channel blockers, diuretics, renin inhibitors, ACE inhibitors, AT-1 receptor antagonists, ET receptor antagonists, and nitrates.

13. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 6 or 7 , or a pharmaceutically acceptable salt or ester, in combination with a pharmaceutically acceptable carrier.

14. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 6 or 7 , or a pharmaceutically acceptable salt or ester thereof, in combination with a pharmaceutically acceptable carrier and one or more pharmaceutical agents.

15. A method of treating obesity comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 or a composition of claim 8 .

16. A method of inducing weight loss comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 or a composition of claim 8 .

17. A method of treating obesity comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 in combination with one or more pharmaceutical agents.

18. The method of claim 17 , wherein the compound of claim 1 and one or more pharmaceutical agents are administered as a single pharmaceutical dosage formulation.

19. A method of treating obesity comprising the step of administering to a subject in need thereof a therapeutically effective amount of a composition of claim 9 , 10 , 11 , or 12 .

20. Trans-(1R,2R)-2-({3′-flouro-4′-,[(6-fluoro-1,3benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 27, 2009
From: BAYER PHARMACEUTICALS CORPORATION
To: BAYER HEALTHCARE LLC
Reel/Frame 023027/0804 →
Continuity (3)
Division 1083983300 · May 6, 2004
Provisional Application 6046961900 · May 9, 2003
Related Publication 20060194859A1 · Aug 31, 2006